The long term objectives are to determine the role of fibroblast growth factors (FGF) in the control of the proliferation and differentiation of the various ocular cell types which are sensitive to it and that of the newly discovered vascular endothelial cell growth factor (VEGF) in the control of proliferation and permeability of retina derived capillary endothelial (RCE) cells. The applicant would analyze whether transfection of iris melanocytes, RPE cells, and RCE cells, with bFRG cDNA expression vector could lead to their autonomous proliferation and ultimate transformation into neoplastic cells. Using both types of transfected cell types, he would first analyze whether bFGF acts intracellularly (as most oncogene products do) or needs to be released by the cells in order to interact with exposed cell surface receptors. Since cell transformation can be the direct result of oncogene expression, the applicant would analyze in transfected cells whether constitutive expression of c fos, and c myc oncogenes can be observed. He would initiate studies on the expression in ocular tissue of VEGF and study its possible participation in proliferative disorders occurring during diabetic retinopathy. To determine if expression of the VEGF gene or FGF gene had any effect during ontogeny, the applicant would inject AHR viruses containing those genes into avial embryos at different stages of development and analyze the occurrence of developmental abnormalities or tumors with the time of injection in ocular tissues. He would study the expression of VEGF in tissue and cells derived from the ocular system. If expressed, VEGF could play a role in controlling developmental processes. He would analyze the ability of VEGF to control events related to the angiogenic process in RCE cells. This includes its chemotactic activity and its ability to stimulate plasminogen activator and collagenase, while repressing plasminogen inhibitor activity. Finally the receptor for VEGF would be defined.
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